Bio-Medical Materials and Engineering 25 (2015) 77–88 DOI 10.3233/BME-141238 IOS Press
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Application of hydrophobic coatings in biodegradable devices Juan Meng a,b , Haiyan Li b , Yaqin Gao a , He Xu b , Hongchen Gu b and Jiang Chang b,c,∗ a
Shanghai MicroPort Medical (Group) Co., Ltd, Shanghai, China Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China c Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, China b
Received 5 November 2013 Accepted 23 June 2014 Abstract. BACKGROUND: Degradation periods of biodegradable medical devices strongly affect their clinical performance and therefore special attention has been drawn to modulate their degradation rate. OBJECTIVE: This paper presents an experimental study on the effect of hydrophobic coating on the degradation behavior of PLLA samples. METHODS: PLLA films were coated with a thin layer of PCL, and a combination of scanning electron microscopy (SEM), Ubbelohde Viscometer Capillary, and chromatograph of gel permeation (GPC) was used to evaluate the morphology and molecular weight changes of samples during degradation. In addition, the mass loss of samples was also measured during the experiment. RESULTS: PLLA samples with PCL coatings showed a slower degradation rate than those without PCL coatings, which indicated that PCL coatings could protect inside PLLA samples and slow down the degradation rate of PLLA samples. CONCLUSIONS: The results of the study suggest that hydrophobic coating on polymer materials is a useful approach to control the degradation of polymer medical device. Keywords: Biodegradable polymer, degradation, coatings, polyesters, morphology
1. Introduction Biodegradable sutures made from polyesters, such as polylactide (PLA) and poly-glycolic acid (PGA) were approved by FDA forty years ago and since then PLA and PGA have been widely used in clinical practices [1,2]. As the processing technique has been actively explored recently, biodegradable polyesters such as PLA, PGA and polycaprolactone (PCL) are attracting more and more attentions in medical devices applications [3]. Traditional applications include the biodegradable sutures [4,5], biodegradable orthopedic implants [2,6,7], drug release systems [8–10] and so on. Recently, biodegradable vascular stents and tissue engineering scaffolds are becoming the subjects of intense studies [11– 13]. *
Address for correspondence: Jiang Chang, Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China. Tel.: +86 21 52412804; E-mail:
[email protected]. 0959-2989/15/$27.50 © 2015 – IOS Press and the authors. All rights reserved
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The degradation period of polyesters may range from a few days to a few years, depending on the molecular weights, types of molecules, crystallization, glass transition temperature, hydrophobicity of monomers and so on [2,4–7,14]. Polyesters are insoluble in water. However, the ester bond can react with water and take hydrolysis reaction. Among polyesters, PCL is most hydrophobic and its degradation period is relatively longer than other polymers. PLA and PGA degrade faster than PCL. However, their mechanical properties are stronger than those of PCL, so they are more widely used in orthopedic and cardiovascular areas than other polymers [12]. The clinical effects of biodegradable medical device were strongly affected by the degradation properties of the device, including degradation rate and period. For example, if the degradation rate of vascular stents is too fast, the blood vessel cannot be supported for enough time, which results in a disappointing TLR (target lesion revascularization) [12]. Several methods have been developed to modulate the degradation rate of medical devices. For example, cross-linkage was used to decelerate the degradation rate of PLA [15]. And the degradation rate of a poly(lactic-co-glycolic acid) copolymer could be slowed down by increasing the component ratio of LA to GA monomers [16]. Surface coating is another method to adjust the degradation rate of biodegradable materials. For example, hydroxyapatite (Ca10 (PO4 )6 (OH)2 ) has been coated on magnesium alloy by ion-beam assisted deposition technique and heat treatment to modify the degradation behavior of magnesium alloy [17]. It was found that PCL polymers could be used to modulate the degradation rate of PLA by blended PCL with PLA [18]. However, blending may also change the mechanical properties of PLA and then affect the functionality of medical device. Compared to blending, surface coating method is easier to be operated and it does not change the main matrix of the medical device. Therefore, in this paper, we developed a PCL coating layer on the PLA surface by Engineered Fluid Dispensing method. In addition, the degradation properties of PLA with PCL coatings were investigated to study whether the PCL coating modified the degradation rate of PLA. 2. Experimental section 2.1. Experimental materials Poly-L-lactide (PLLA) was purchased from Purac Biomaterials (the Netherlands). PCL, chloroform (AR), tetrahydrofuran (THF) (AR), potassium dihydrogen phosphate (AR) and disodium hydrogen phosphate (AR) were purchased from Sinopharm Chemical Reagent Co., Ltd. 2.2. Preparation of PLLA coupons Five grams of PLLA particles were dissolved in 150 ml chloroform in beaker flask and the solution was stirred for 12 hours. Then the solution was pooled into a rectangular mold (INNER SIZE: L × W × H = 15.5 cm × 7 cm × 5 cm). The mold and the solution were then put in the vacuum oven to remove the air bubbles from the solution. During this process, the vacuum should be slowly turned on to protect the solution from “boiling” until the vacuum reached −0.1 MPa. Then, the solution was kept in this vacuum overnight. The solution was moved to the fuming hood after totally dried in the vacuum. After the samples were air-dried until constant weight, the samples were cut into small coupons with 5 × 40 mm (W × L) dimensions. Then each sample was weighted by electronic analytical balances (Sartorius, Göttingen, Germany) before coating and degradation experiments. The weight of each sample was recorded and data were labeled as W0 .
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Fig. 1. Sketch of coating system and pictures of samples. (a) Sketch of coating system; (b) Picture of coated sample immersed in test tube for degradation test; (c) Picture of blank sample; (d) Picture of coated sample. (Colors are visible in the online version of the article; http://dx.doi.org/10.3233/BME-141238.)
2.3. Preparation of coated samples 0.04 g PCL particles were dissolved in 10 ml chloroform to make 4% solution and the solution was sprayed on the PLLA coupons by EFD (Engineered Fluid Dispensing) coating system (Nordson EFD, RI 02914, USA). The sketch of coating system is shown in Fig. 1(a). The coated coupons were dried in vacuum oven until constant weights. Each sample was weighted by electronic analytical balances before degradation experiments. The weight of each sample was recorded and data were labeled as W1 . The weight increase from W0 to W1 for each sample corresponds to the weight of coating layer on each coupon, which was about 10 mg. 2.4. Materials characterization Before and after coating process, the samples were attached to a glass slide and a Contact angle measurement system (KRUSS, KRUSS GmbH, Germany) was used to measure the contact angles between the sample and pure water droplet. Scanning Electron Microscopy (SEM, FEI, QUANTA, the Netherlands) was used to characterize the surface topography of the samples. Chromatograph of gel permeation (GPC, Waters e2695/2414, Waters, US) was used to analyze the molecular weight of the polymers. Briefly, 10 mg of sample was dissolved in 10 ml chloroform for testing. A serial of standard polystyrene
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substances were used as references. The flow speed was 1.0 ml/min and the temperature was 35◦ C during test. Chromatographic columns were Mono GPC-300, Mono GPC-500 and Mono GPC-1000. The samples were also dissolved in chloroform (0.1 g/ml) for inherent viscosity test by using Ubbelohde Viscometer Capillary. 2.5. In vitro degradation experiments 2.5.1. Preparation of degradation solution The degradation solution was prepared based on ISO 15814:1999. Briefly, the following two solutions were prepared first: solution (a) 9.078 g potassium dihydrogen phosphate was dissolved in 1 l water and solution (b) 11.876 g disodium hydrogen phosphate was dissolved in 1 l water. Then 18.2% solution (a) and 81.8% solution (b) were mixed to get the degradation solution with PH value of 7.4 ± 0.2. 2.5.2. Experimental grouping Samples were divided into two groups. One group included 24 PLLA coupons coated with PCL polymers (coated samples). The other one included 24 PLLA coupons without any coatings (blank samples). Each sample was weighed, put in a separate test tube and immersed by 30 ml degradation solution (shown in Fig. 1(b)). The test tubes were statically stored in 37◦ C incubator for degradation. At different time points of 0 week, 1 week, 2 weeks, 4 weeks, 12 weeks and 24 weeks, 4 samples in each group were took out of the tube. For samples at time point of 0 week, each sample was weighted by electronic analytical balances directly. For degraded samples, each sample was rinsed with distilled water for three times after degradation period and dried in the vacuum oven to constant weight. Then each sample was weighted by electronic analytical balances. And the weight of degraded sample was recorded and the data were labeled as W2 . The weight of the degraded sample divided by the weight of the same sample before degradation gave the mass loss percentage data. For each blank sample, mass loss was obtained by dividing W2 by W0 . Similarly, for each coated sample, mass loss was obtained by dividing W2 by W1 . After mass measurements, 3 of the 4 dried coated samples were washed by THF a few times to dissolve the coated PCL in THF. The THF solution were then collected and evaporated to get the PCL coating materials. After THF evaporated, the PCL polymers were collected from the solutions and molecular weights and inherent viscosity of PCL were measured by GPC. The samples used in each characterization are listed in Table 1. Table 1 List of samples used in different characterizations #1
Blank samples #2 #3 #4
√
√
SEM
√
√
Inherent viscosity
NA
NA
Mass
GPC
√
√
NA √
NA √
√
Coated samples Coating removed Coatings #2 #3 #4 √ √ √ √
√
√
NA
NA
#1
NA √
NA √
NA NA √
NA NA NA NA NA NA NA NA √ Notes: “ ” means that the sample was used in this characterization; “NA” means that the sample was not used in this characterization.
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2.6. Statistical analysis The mass loss data was analyzed to check whether the mass loss change rate of coated samples is significantly different from blank samples. Since the sample size is small (n = 4 for each group at each time point), Mann–Whitney test was applied to compare the data by using Minitab software (Suite 1113, Silver Tower, 933 Zhong Shan West Road, Shanghai). The confidence interval was set to be 95% and a p value of
